Recent experimental studies of increases in smoking behavior in man after drinking ethanol have validated the frequent and long-standing reports of correlations between smoking and drinking in the general population. The proposed research will investigate the behavioral and pharmacological aspects of the interaction between these two licitly abused drugs under the more controlled conditions occurring in an animal preparation. Using the intravenous self-administration of nicotine by monkeys as a model of smoking in humans, the effects of ethanol, caffeine, and an illicitly abused drug, d-amphetamine, will be examined on the rate of nicotine intake. These studies will be done under conditions where few external stimuli are present (fixed-ratio schedule), and where a number of stimuli correlated with nicotine injections are programmed (second-order schedule). An identical schedule of food reinforcement will be incorporated in all phases of the experiment to allow the assessment of drug effects not specific to nicotine. In order to evaluate drug interactions at the level of biotransformation, the pharmacokinetics of nicotine plasma concentration will be determined before and during the administration of ethanol, with the plasma concentrations of ethanol also being measured.